System and method for minimally invasive disease therapy

ABSTRACT

A system for treating a lesion site of a patient is disclosed. The system includes a cannula having a lumen, a conduit in communication with said lumen, an introducer stylet removably disposed within said cannula, a resecting device selectively insertable within said cannula, and an adjuvant treatment device selectively insertable within said cannula.

RELATED APPLICATIONS

The present application is a continuation in part application of U.S.patent application Ser. No. 11/237,110 filed on Sep. 28, 2005, entitled“System and Method for Minimally Invasive Disease Therapy,” the contentsof which are incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to a surgical system and methodfor removing and treating diseased tissue and more particularly to aminimally invasive system and method for removing diseased tissue andcreating a margin around an excised area.

BACKGROUND Description of the Related Art

Surgical cancer treatments have advanced to two primary stages. A firststage removes the cancerous tissue by resecting the tissue from thebody. The goal of the first stage is to remove all cancerous cells froma target area. However, unless a large portion of healthy tissue is alsoresected, a possibility exists that some cancerous cells remain near theresection site.

A second stage typically involves a broad-based radiation therapy to thecancerous region. The radiation therapy is necessary to destroy anycancerous tissue that may have remained in the targeted area afterresection. However, broad-based radiation therapy requires multipleexposures to high doses of radiation. Such exposure results inundesirable side effects and the exposure may not be limited to thetissues that surrounded the resected tissue. Further, a full course oftreatment may require six weeks of individual treatments that result infrequent visits to a hospital or treatment suite.

Accordingly, an improved treatment method is desired that improvestreatment effectiveness, reduces side effects, reduces treatment time,avoids widespread exposure to radiation, and is verifiable using medicalimaging techniques. Additionally, an improved treatment method isdesired that may be used with multiple imaging modalities, thesemodalities may include Magnetic Resonance Imaging (MRI), ultrasound, andx-ray Computed Tomography (CT).

SUMMARY

A system for treating a lesion site of a patient is disclosed. In oneembodiment the system includes a cannula having a lumen, a conduit incommunication with the lumen, an introducer stylet removably disposedwithin the cannula, a resecting device selectively insertable within thecannula, and an adjuvant treatment device selectively insertable withinthe cannula. In an alternative embodiment, a tissue cavity is subject tobrachytherapy.

A method of treating a lesion site of a patient is also disclosed. Themethod includes the steps of inserting an introducer stylet having anouter cannula disposed thereon into a patient's body creating a pathwayto a lesion site, removing the introducer stylet from the patient's bodyleaving behind the outer cannula. The method may further includeinserting a resection device into the patient's body through the outercannula and removing tissue from the lesion site, removing the resectiondevice from the patient's body leaving behind the outer cannula.Further, the method may include inserting an adjuvant therapy deviceinto the patient's body through the outer cannula, and treating thelesion site using the adjuvant therapy device.

BRIEF DESCRIPTION OF THE DRAWINGS

The features and inventive aspects of the present invention will becomemore apparent upon reading the following detailed description, claims,and drawings, of which the following is a brief description:

FIG. 1 is a side view of an introducer stylet in accordance with anembodiment of the present invention;

FIG. 2 is a side view of an outer cannula and fluid conduit inaccordance with the embodiment of FIG. 1;

FIG. 3 is a side view of a target confirmation device in accordance withthe embodiment of FIG. 1;

FIGS. 3A and 3B are side views of target confirmation devices accordingto alternate embodiments of the present invention;

FIG. 4 is a side view of an exemplary biopsy device for use with anintroduction system of the present invention;

FIG. 5 is a detailed cross sectional view of a cutting element of thebiopsy device of FIG. 4;

FIG. 6 is a side view of an aspiration wand suitable for insertion intothe outer cannula of FIG. 2;

FIG. 7 is a side view of a treatment device wand suitable for insertioninto the outer cannula of FIG. 2;

FIG. 8 is a cross-sectional view of a cryo-ablation treatment device foruse with the treatment device wand of FIG. 7;

FIG. 9 is a cross-sectional view of the cryo-ablation treatment deviceof FIG. 8 as used in a medical procedure;

FIG. 10 is a cross sectional view of a photodynamic treatment device foruse with the treatment device wand of FIG. 7;

FIG. 11 is a side view of a radiofrequency treatment device for use withthe treatment device wand of FIG. 7;

FIGS. 12-21 are elevational views illustrating different stages of amedical procedure using the medical system of the present invention.

FIG. 22 is a haemostatic agent embodiment that introduces a haemostaticagent to a target site, according to an embodiment;

FIG. 23 is an alternative haemostatic agent embodiment to the embodimentof FIG. 22 that introduces a haemostatic agent to a target site;

FIG. 24 is a procedure introducing an inking agent to a target site,according to an embodiment;

FIG. 25 is an inked margin region around the periphery of a target site;

FIG. 26 is a resection of a target site including an inked marginregion;

FIG. 27A is a fully inked portion of resected tissue;

FIG. 27B is a partially inked portion of resected tissue;

FIG. 27C is a fully non-inked portion of resected tissue;

FIG. 28 is a target site after inking and resection to remove an inkedmargin region;

FIG. 29 is a flow diagram of a resection process, including applicationof a haemostatic agent as is described above with respect to FIGS. 22and 23;

FIG. 30 is a margin process for determining whether a margin region hasbeen resected, and is related to FIGS. 24-28;

FIG. 31 is a contrast agent localization process wherein contrast agentsare used in conjunction with imaging modalities and a targetconfirmation device to verify therapy positioning;

FIG. 32 is a contrast agent therapy verification process wherein alesion is identified, treatment is performed, and treatment is verifiedusing a selected imaging modality;

FIG. 33 is an attempt to position an outer cannula centrally withrespect to a lesion;

FIG. 33A is a portion of FIG. 33 that has been enlarged to show thepositioning attempt;

FIG. 34 is a center-of-mass placement of a target;

FIG. 35 is a partially treated region within a lesion;

FIG. 36 is a completed region, after a lesion is fully treated;

FIG. 37 is a re-injection process that provides for removal of canceroustissue, denaturing the protein contained therein, and re-injecting theprotein to stimulate the body's natural immune response against thecancerous cells.

FIG. 38 shows placement of a localized treatment seed (e.g.,brachytherapy);

FIG. 39 shows a treatment penetrating the surrounding tissue using asingle localized treatment seed;

FIG. 40 shows placement of multiple treatment seeds at a target site;

FIG. 41 shows a treatment penetrating the surrounding tissue usingmultiple localized treatment seeds;

FIG. 42 shows a tissue anchor for a localized treatment seed within apatient;

FIG. 43A shows a side cross-section of treatment pellets dispersed in amaterial;

FIG. 43B shows a front cross section of treatment pellets dispersed in amaterial;

FIG. 43C shows front cross section of treatment pellets dispersed in amaterial in an alternative embodiment, the pellets being evenly spacedapart;

FIG. 44 shows a caged treatment seed;

FIG. 45 shows a caged treatment seed wherein the cage includes barbssuch that the cage and seed do not migrate once deployed;

FIG. 46 shows a compressed foam capsule being delivered to the targetsite;

FIG. 47 shows a delivered foam capsule at the target site;

FIG. 48 shows an expanded foam capsule substantially filling the targetsite;

FIG. 49 shows a treatment penetrating the surrounding tissue using anexpanded foam delivery mechanism;

FIG. 50 shows the deployment and placement of treatment seeds around thedebulked area; and

FIG. 51 shows a flow diagram of deployment and placement of one ormultiple treatment seeds at the debulked area.

DETAILED DESCRIPTION

Referring now to the drawings, preferred embodiments of the presentinvention are shown in detail. Although the drawings representembodiments of the present invention, the drawings are not necessarilyto scale and certain features may be exaggerated to better illustrateand explain the present invention. The embodiments set forth herein arenot intended to be exhaustive or otherwise limit the invention to theprecise forms disclosed in the following detailed description.

Referring to FIGS. 1-3, a medical system 20 is shown that includes anintroducer stylet 22, an outer cannula 24 and a target confirmationdevice 26. As will be described in detail, system 20 is particularly,but not necessarily, suited for use in biopsy procedures that identifythe target biopsy site using Magnetic Resonance Imaging (MRI) or acomparable medical imaging modality. A system similar to system 20 canbe seen by way of example in pending U.S. patent application Ser. No.10/649,068, which is owned by the assignee of the present invention andis incorporated herein by reference in its entirety.

In one embodiment, introducer stylet 22 includes a handle 28 and astylet 30 having a distal end 32 and a proximal end 34 connected tohandle 28. Handle 28 may be made of a medical grade resin or other MRIcompatible material. Stylet 30 may also be made of an MRI compatible,medical grade material, such as 316 stainless steel or inconel 625.

In one particular configuration, distal end 32 of stylet 30 may beprovided with a tissue piercing tip, such as a trocar tip, to facilitatepenetration of stylet 30 into a patient's tissue. In addition to atrocar tip, it will be appreciated that stylet 30 may include otherdevices for piercing the patient's tissue, including without limitation,devices that use a laser, radiofrequencies (RF), or ultrasonics topierce the tissue. The length of stylet 30 is generally denoted by thereference character “A” in FIG. 1.

Referring to FIG. 2, an embodiment of outer cannula 24 is shown. Outercannula 24 extends from an open proximal end 36 to an open distal end38, which is separated from proximal end 36 by a distance generallydenoted by the reference character “B”. Like introducer stylet 30, outercannula 24 may be made from a medical grade resin or other MRIcompatible material. In some configurations, proximal end 36 may includea luer-style fitting or other suitable configuration for interfacing,but not necessarily connecting, outer cannula 24 with targetconfirmation device 26. A depth limiting member 39, such as, forexample, a rubber o-ring, may be moveably disposed on outer cannula 24to limit the insertion depth of outer cannula 24 into the patient'sbody.

In one embodiment, outer cannula 24 may also include an inner lumen 40therethrough, which is open to communication with a fluid conduit 42 forsupplying fluids, such as saline and anesthetics, or removing fluids,such as blood, from the patient's body. Fluid conduit 42 communicateswith inner lumen 40 via a port in outer cannula 24. In someconfigurations, outer cannula 24 may include a haemostatic valve,depicted generally as element 41, or a manually operable valve 41′ thatcan be selectively closed to prevent the escape of fluid from proximalend 36. Fluid conduit 42 may also include a directional valve 43 toselectively control the supply and removal of fluid to and from innerlumen 40, respectively.

In FIG. 3, an embodiment of target confirmation device 26 is depicted.Target confirmation device 26 is an elongated member that is sized tofit within inner lumen 40 of outer cannula 24. Target confirmationdevice 26, which may be made of a medical grade resin or other MRIcompatible material, extends from a connecting end 44 to a distal end46. Connecting end 44 may be configured with a cap 47 that abutsproximal end 36 of outer cannula 24 when target confirmation device 26is inserted into outer cannula 24. In some configurations, cap 47 mayinclude a luer-style fitting or other suitable feature for interfacing,but not necessarily connecting, target confirmation device 26 with outercannula 24.

Distal end 46 of target confirmation device 26 may be generally roundedto facilitate entry into the patient's body. In one embodiment, aportion of target confirmation device 26 is configured with a magneticresonance imaging (MRI) identifiable material, such as inconel 625,titanium or other material with similar magnetic characteristics. In oneparticular configuration, a targeting band 48 is provided a distance “C”from connecting end 44, as shown in FIG. 3; the distance “C” beingmeasured from the approximate center of targeting band 48 to connectingend 44 (or the inside of cap 47), for example. Targeting band 48provides a reference point in an MR image relative to the target biopsytissue.

In another embodiment of target confirmation device 26, the tip oftarget confirmation device 26 itself may be used to provide thereference point in the MR image, provided the target confirmation devicematerial exhibits a relatively low artifact during MR imaging. As usedherein, the term “artifact” describes a material's tendency to distortan MR image. A material exhibiting a relatively high artifact willrender the body tissue surrounding the material unreadable in an MRimage. Conversely, a material with a relatively low artifact or signalvoid will allow the material to be readily identified in the MR imageand will not significantly distort the MR image of the surroundingtissue.

As shown in the embodiments of FIGS. 3A and 3B, distal end 46′, 46″ oftarget confirmation device 26′, 26″ may include a particular shape tohelp identify the location of target confirmation device 26 relative tothe surrounding tissue. In the embodiment of FIG. 3A, a portion oftarget confirmation device 26′ adjacent distal end 46′ has a smallerdiameter relative to the remaining length. Alternatively, in theembodiment of FIG. 3B, a portion of target confirmation device 26″ has atapered distal end 46″ to provide an hour glass like image when viewedunder MR. It will be appreciated that the target confirmation devicesrepresented in FIGS. 3, 3A and 3B are not limited to the configurationsshown, and that other configurations are with in the scope of thepresent invention.

In still another embodiment, stylet 30 may function as a targetconfirmation device. In this embodiment, introducer stylet 22, and moreparticularly stylet 30, may be made of an MRI compatible material thatpreferably, but not necessarily, exhibits a relatively low artifact.

An exemplary resection apparatus 50, which is suitable for use withsystem 20 of the present invention, is generally shown in FIG. 4 and inmore detail in FIG. 5. Resection apparatus 50 includes a cutting element52 sized for introduction into a handpiece 54. The exemplary resectionapparatus 50 is configured as a “tube-within-a-tube” cutting device.More particularly, cutting element 52 includes an outer cannula 56having an outer lumen 57 and an inner cannula 58 sized to fitconcentrically within the outer lumen. A motor or other motiongenerating device is provided within handpiece 54 to rotate and/ortranslate inner cannula 58 within outer cannula 56. A biopsy apparatussimilar to resection apparatus 50 can be seen by way of example inpending U.S. patent application Ser. Nos. 09/707,022 and 09/864,031,which are owned by the assignee of the present invention and areincorporated herein by reference in their entirety.

One embodiment of a working end of cutting element 52 is depicted inFIG. 5. In the illustrated embodiment, outer cannula 56 defines atissue-receiving opening 60, which communicates with outer lumen 57. Theworking end of cutting element 52 may further include a cutting board 64that is disposed within outer lumen 57 at the distal end of outercannula 56. Inner cannula 58 defines an inner lumen 65 that is hollowalong its entire length to provide for aspiration of the biopsy sample(tissue). Inner cannula 58 terminates in a cutting edge 66 that may beformed by an inwardly beveled surface having a razor-sharp edge.

Referring to FIG. 6, a wand 68 is shown that can be inserted into outercannula 24 after resection apparatus 50 has been removed, or at any timeouter cannula 24 is free of obstruction. In one embodiment, wand 68extends from a connecting end 70 to an insertion end 72 and includes alumen 74 that extends from connecting end 70 to insertion end 72.Connecting end 70 may include a luer interface or other suitable fittingfor connecting wand 68 to a vacuum source (not shown) or a fluid source(not shown). Wand 68 may also include a cap 76 that can be placed ontoconnecting end 70 to inhibit fluid leakage when wand 68 is inserted intothe patient. The haemostatic valve 41 in outer cannula 24 seals againstwand 68, as it does against target confirmation device 26 and resectionapparatus 50, when inserted into outer cannula 24. Additionally, theoutside diameter of wand 68 is preferably less than the inside diameterof inner lumen 40 to allow the passage of fluids through fluid conduit42 to pass into or out of the patient's body. When cap 76 is removed andwand 68 is connected to a vacuum source, fluids, such as blood andsaline, can be aspirated from the biopsy site or, conversely, whenconnected to a fluid source, fluids can be delivered to the biopsy site.

Referring to FIG. 7, a treatment device 100 is shown that can beinserted into outer cannula 24. In one embodiment, treatment device 100includes a treatment tip 102 sized for introduction into the patient'sbody, a treatment shaft 104 having a proximal end 106, and a treatmenthandpiece 108. A fluid system, electrical system, or other supportingelements may be attached to, or operate in cooperation with, treatmenthandpiece 108 in order to effectuate an adjuvant treatment at treatmenttip 102 (to be explained in further detail with respect to FIGS. 8-11).

An alternative embodiment of treatment device 100′ is depicted in FIG.8. Treatment device 100′ is a cryo-ablation device. Treatment device100′, utilizing cryo-ablation, is a surgical technique using extremelycold temperatures to destroy cells. In the illustrated embodiment,treatment device 100′ includes an inner cannula 120 sized to fit withinouter cannula 24 of system 20. Treatment tip 102′ is sized to extendbeyond distal end 38 of outer cannula 24 and directly interface thepatient's tissue. A supply tube 122 extends from treatment handpiece108′ through inner cannula 120 and provides freezing liquid to treatmenttip 102′. The freezing liquid exits treatment tip 102′ through a returncavity 124 defined as a region between inner cannula 120 and supply tube122. Treatment tip 102′ is configured to directly interface thepatient's tissue and deliver the freezing treatment to the tissuesurrounding treatment tip 102′.

Additionally, treatment tip 102′ may include a shield 126 that allowsfor a portion of the tissue surrounding treatment tip 102′ to besubstantially protected from the freezing treatment. Thus, a surgeon mayuse shield 126 in sensitive areas so that undesired damage does notoccur to sensitive tissues. For example, as illustrated in more detailin FIG. 9, treatment tip 102′ is used between a target tissue 130 and aprotected tissue 132. In this example, a surgeon may intend targettissue 130 to receive the cryo-ablation from treatment tip 102′.However, a sensitive tissue, such as an intestinal wall or skin, may notbe able to withstand the treatment. In the case of an intestinal wall,the freezing may create an opening that may cause leakage and infection.Similarly, the skin may become damaged and a breaking of the skin mayresult. In these cases, shield 126 insulates protected tissue 132 fromthe freezing effects.

Another alternative embodiment of treatment device 100″ having treatmenttip 102″ is embodied as a photodynamic treatment device 140 asillustrated in FIG. 10. Photodynamic treatment device 140 includes asupport shaft 142 sized to fit within outer cannula 24 of system 20, aballoon 144 configured for inflation when extended beyond outer cannula24 of system 20, an optic guide 146 configured to deliver light, and acap 148 configured to secure balloon 144 and optic guide 146 at a distalend 150. Photodynamic treatment device 140 utilizes a light source and,if desired, a photosensitizing agent to effectuate destruction of tissueat a desired location.

In operation, balloon 144 is inflated by a high pressure provided by aninflation channel 151 positioned between optic guide 146 and supportshaft 142. Once inflated, balloon 144 is pressed against the surroundingtissue and a high power light source is activated. Photodynamictreatment device 140 then provides emitted light 152 to the treatmentlocation. The heating effects of emitted light 152 may alone besufficient for treatment. However, if desired, a photosensitizing agentmay be applied to the treatment location to improve the destructiveeffect of emitted light 152. The photosensitizing agent may be appliedbefore the surgical procedure, or alternatively, be applied locally bywand 68. When a photosensitizing agent is used, emitted light 152interacts with the agent providing enhanced tissue destruction. Further,the photosensitizing agent may be configured to have an affinity forcancerous cells. Thus, damage to healthy tissues is further reduced.

Another alternative embodiment of treatment device 100′″ havingtreatment tip 102′ is a radiofrequency ablation device 160 asillustrated in FIG. 11. Radiofrequency ablation device 160 includes adelivery cannula 162 sized to fit within outer cannula 24 of system 20and one or more probes 164 configured to deliver radiofrequency energyto surrounding tissue. When inserting delivery cannula 162 in outercannula 24 of system 20, probes 164 are retracted within deliverycannula 162. After reaching the appropriate depth to access thetreatment location, probes 164 are extended beyond a distal end 166 ofdelivery cannula 162. After extension, probes 164 are in communicationwith the surrounding tissue and may be energized to effectuatetreatment.

Yet another alternative embodiment of treatment device 100 includes alaser ablation device that utilizes heat to ablate tissue.

Still another alternative embodiment of treatment device 100 includesthe use of localized interstial brachytherapy. In using this approach, aradioactive substance is provided interstially via balloon systems, oneor more radioactive seeds, or the like, which may be placed (eithertemporarily or permanently) at the suspect tissue.

Referring to FIGS. 12-21, a medical procedure of the present inventionwill be described. In one embodiment, system 20 is employed to provideadjuvant treatment of a target tissue 80 within a patient's body 170.Target tissue 80, or lesion, to be biopsied and/or removed andsubsequently adjuvantly treated is located using a medical imagingsystem, such as MRI or other suitable imaging modalities. A referencestructure 172 may be positioned adjacent patient's body 170 to assist inlocating the target tissue 80. The location of target tissue 80 relativeto reference structure 172 may be determined along one or more axes. Inthe illustrated embodiment, the location of target tissue 80 relative toreference structure 172 is determined along the X and Y axes; however,the target tissue 80 location may also be determined along all three ofthe X, Y, and Z axes. While the described method employs referencestructure 172 to locate target tissue 80, reference structure 172 is notnecessarily required and a more “free-hand” approach may be utilized.

In an embodiment, reference structure 172 includes a support grid havinga number of holes therethrough. Each hole is sized to allow passage ofouter cannula 24. The hole through which outer cannula 24 is ultimatelyinserted is determined by the location of target tissue 80 relative toreference structure 172 along the X and Y axes. Patient's body 170 andreference structure 172 are viewed using a medical imaging system, suchas MRI, to determine the location of target tissue 80 relative toreference structure 172.

After application of anesthesia, the stylet portion of introducer stylet22 and a portion of outer cannula 24 are inserted through the supportgrid and into patient's body 170, creating a pathway 180 to targettissue 80 (see, e.g., FIG. 12). Introducer stylet 22 is then removedfrom patient's body 170 leaving behind outer cannula 24 and pathway 180(see, e.g., FIG. 13).

Fluids may be inserted into or removed from patient's body 170 throughinner lumen 40 via fluid conduit 42. These fluids may include, forexample, additional anesthetics and/or saline solution to cleansepathway 180 and remove blood. Accumulated blood and other fluids withinpathway 180 may be aspirated through fluid conduit 42 or by insertingwand 68 prior to insertion of target confirmation device 26, 26′, 26″.

Once introducer stylet 22 is removed from outer cannula 24, targetconfirmation device 26, 26′, 26″ may be inserted into patient's body 170through the path 180 created by outer cannula 24 (see, e.g., FIGS. 13and 14). With target confirmation device 26, 26′, 26″ properly insertedinto outer cannula 24, an image of the target site is again taken todetermine the location of targeting band 48 or distal end 46′, 46″ inrelation to target tissue 80 and reference structure 172. If targetingband 48 or distal end 46′, 46″ is in the desired position adjacenttarget tissue 80 along the Z-axis, target confirmation device 26, 26′,26″ is removed from outer cannula 24. However, if targeting band 48 ordistal end 46′, 46″ is not in the desired position, then the position oftarget confirmation device 26, 26′, 26″ and outer cannula 24 is modifiedalong the Z-axis until the desired position is achieved.

Once the desired position is achieved, depth limiting member 39 is movedagainst reference structure 172 to inhibit movement of outer cannula 24further into patient's body 170. When no reference structure 172 isused, depth limiting member may be moved directly against the patient'sskin. Target confirmation device 26, 26′, 26″ is then removed from outercannula 24 and resection apparatus 50 is inserted into outer cannula 24until handpiece 54 abuts proximal end 36 of outer cannula 24.

In the embodiment illustrated in FIG. 15, one or more samples of targettissue 80 are removed from patient's body 170 through tissue-receivingopening 60. The correct position of tissue-receiving opening 60 isensured because the distance “C” between connecting end 44 of targetconfirmation device 26, 26′, 26″ and targeting band 48 (see, e.g., FIGS.3 and 14), or the distance between connecting end 44 and thepredetermined location on target confirmation device 26, 26′, 26″ (FIGS.3, 3A, 3B), is approximately equal to the distance between the center oftissue-receiving opening 60 and handpiece 54 of resection apparatus 50.

FIG. 16 illustrates the use of resection apparatus 50 for debulking aregion of tissue where target tissue 80 is a significant region. In thiscase, resection apparatus 50 may be rotated and used to debulk theentire region of target tissue 80. As illustrated, resection apparatus50 has been rotated leaving a void 182 having an inner wall 183, and isused to resect the remaining portion of target tissue 80.

Generally, the debulking procedure may be used where suspicion ofcancerous tissue exists, or where treatment of a previously resectedregion is desired. In the case where a biopsy has previously been taken,the debulking process removes any hematomas that may have developed dueto the biopsy or earlier procedure. In addition to resection of suspecttissues, removal of fluids and hematomas improves the efficacy of theadjuvant treatment because any fluids or hematomas act as insulators toadjuvant treatment such as cryo-ablation and reduce the effectiveness ofthe freezing penetration.

When resection of target tissue 80 is complete, resection apparatus 50is removed from patient's body 170 leaving void 182 (see, e.g., FIG.17). Treatment device 100, 100′, 100″, 100′″ may then be inserted intopatient's body 170 through outer cannula 24 (see, e.g., FIGS. 7 and 18).Treatment tip 102, 102′, 102″, 102′″ is correctly positioned within void182 because the distance “C” between connecting end 44 of targetconfirmation device 26, 26′, 26″ and targeting band 48 or distal end46′, 46″ (see, e.g., FIGS. 3 and 14) is approximately equal to thedistance between the center of tissue-receiving opening 60 and handpiece54 of resection apparatus 50, and is approximately equal to the distancebetween a predetermined portion of treatment tip 102, 102′, 102″, 102′″and treatment handpiece 108 of treatment device 100, 100′, 100″, 100′″(FIG. 7).

With treatment device 100, 100′, 100″, 100′″ inserted into patient'sbody 170 (see FIG. 18), a vacuum device 190 may be attached to fluidconduit 42 by a vacuum hose 192 (see FIG. 19A). A surgeon may thenoperate vacuum device 190 to create a vacuum though lumen 40 of outercannula 24. The vacuum through lumen 40 draws tissue close to opendistal end 38 and collapses void 182 around treatment tip 102, 102′,102″, 102′″. FIG. 19B illustrates the collapsing of void 182 aroundtreatment tip 102, 102′, 102″, 102′″. A gap 200 between treatment tip102, 102′, 102″, 102′″ and outer cannula 24 provides a path for thevacuum to collapse void 182.

Once void 182 has collapsed under the vacuum, treatment tip 102, 102′,102″, 102′″, is activated (see FIG. 20A). The resulting damage to thesurrounding tissue creates a margin 210 of ablated tissue that resultsin an increased success rate for treatment. FIG. 20B illustrates indetail margin 210 surrounding treatment tip 102, 102′, 102″, 102′″ afterthe adjuvant treatment has been applied. The cells in margin 210 havebeen ablated and no longer pose a threat of continued growth ofcancerous cells that may have been interstially surrounding targettissue 80.

After the adjuvant treatment has been applied, the surgeon may removetreatment device 100, 100′, 100″, 100′″. Depending upon the type ofadjuvant treatment applied through treatment tip 102, 102′, 102″, 102′″,a post-treatment void may remain even after treatment device 100, 100′,100″, 100′″ is removed from patient's body 170. The surgeon may thenreview margin 210 under a preferred imaging modality. If, for example,it is determined that the margin is not correctly positioned or theadjuvant treatment has not achieved the appropriate margin 210,treatment may be continued by applying the adjuvant treatment repeatedlyuntil medical imaging satisfactorily verifies the margin. Alternatively,margin 210 may be improved by repeating the procedure or a portion ofthe procedure beginning from any step. Further, the procedure may berepeated a predetermined number of times in order to reach an effectivemargin depth or shape.

After completion of the procedure, void 182 may be aspirated using wand68. During or after aspiration, if any aspiration is desired, a finalimage of margin 210 may be taken to confirm removal of target tissue 80.The imaging also provides a record of the ablation zone for furtheranalysis. Finally, an MRI identifiable treatment site marker, a collagenplug, or other medical treatment may be inserted into the biopsy sitethrough outer cannula 24.

Among other features, the medical system of the present inventionlocalizes the target site in a manner that provides for confirmation ofthe target site under MRI or other visualization modality, and allowspositioning of a resection device to ensure the cutting element of theresection device can be accurately placed at the target site. Further,the medical system provides for accurate positioning of an adjuvanttherapy device. Additionally, the system provides for verification of amargin created by an adjunctive therapy.

The medical system of the present invention also reduces side effectsrelated to cancer treatments. Because the system uses accurate targetedtreatment of the target site, the overall time the time of treatment issignificantly reduced as compared with traditional radiation therapy.Further, there is no widespread exposure to radiation.

While the method is preferably suited for treatment of cancerous tissuesthat are unifocal, the treatment apparatus and method described hereinmay be used for any type of treatment including, but not limited to,multifocal diseases.

FIG. 22 shows a haemostatic agent embodiment 400 that introduces ahaemostatic agent (represented by arrow(s) H) to target site 182 throughvalve 43 and fluid conduit 43. A syringe 401 (or other suitableapplicator) is attached via a connecting tube 402 to fluid conduit 42.Haemostatic agent H is transported along a lumen 404 formed betweenouter cannula 56 and inner lumen 40 of outer cannula 24. Check valve 41functions to prevent haemostatic agent H from exiting outer cannula 24at proximal end 36. Haemostatic agent H is then deployed at 406 totarget site 182 topically, e.g., haemostatic agent H is applied to asurface of target site 182. Once haemostatic agent H is deployed at 406,a haemostatic region 408 is formed that reduces, or in some cases,prevents bleeding into target site 182. Alternatively, haemostatic agentH may be introduced to target site 182 through an introducer, a sideport, through a lumen, or through a resection device or treatment deviceitself.

In controlling the bleeding at target site 182, the effectiveness andefficiency of therapies delivered to target site 182 are improved. Ingeneral, the unknown insulative properties of bleeding are controlledsuch that a more precise, predictable, and reliable treatment results.In one example, cryogenic probe 102 (described in detail above withrespect to FIGS. 7-9 and 19A-21) is used to ablate tissue surroundingtarget site 182. However, the efficiency of the ablation proceduredepends significantly on the rate and quantity of energy transferbetween probe 102 and the surrounding tissue. Where no haemostatic agentH is applied before ablation, target site 182 will continually bleedafter resection apparatus 50 is removed. Thus, when probe 102 isinserted to perform the ablation procedure, the blood at target site 182will become coagulated or hardened when exposed to probe 102. This maypresent a serious problem in an ablation procedure because coagulatedblood behaves as an insulator between probe 102 and the surroundingtissues (see FIG. 19B). Due to the insulative properties of the blood,less energy transfer is performed between probe 102 and the surroundingtissue. The result is that the ablation procedure is less effective andmargin 210 (see FIG. 20B) is reduced.

Other alternative uses for deploying haemostatic agent H includeclotting a free flowing bleeder, e.g. to control significant blood loss.Moreover, stopping or reducing blood flow allows for heated and freezingadjuvant therapies to be applied with reduced heat sink effect fromflowing blood that carries away heat or cold. In addition, haemostaticagent H may be used to dilute or flush out fluids that may becongregated near target site 182 while at the same time providingcontrol for bleeding.

With the deployment of haemostatic agent H to target site 182, blooddoes not flow from the walls of target site 182. The result is improvedperformance from an ablation procedure using probe 102. By reducing orpreventing bleeding from the surrounding tissue, the efficiency of theablation procedure is improved resulting in an improved margin 210(i.e., ablation of margin 210 in its entirety, or at least a greaterdepth of ablation than would have been possible if blood were presentaround probe 102).

FIG. 23 shows an alternative haemostatic agent embodiment 420introducing a haemostatic agent H to target site 182 through proximalend 36 and valve 41. In this embodiment, handpiece 54 is removed fromouter cannula 24 and thus, inner lumen 40 is unrestricted (See FIG. 2).Here, syringe 401 is inserted through proximal end 36 and valve 41 suchthat haemostatic agent H is deployed directly down inner lumen 40 alongpath 424 (See also FIG. 2). When reaching distal end 38 of outer cannula24, haemostatic agent H is deployed at 426 to target site 182. In sodoing, haemostatic region 408 is formed on an inner wall of target site182. Depending upon the type and/or form of haemostatic agent H used,selection of a haemostatic deployment embodiment may be selected. Forexample, a liquid haemostatic agent H may perform well using either theembodiment of FIG. 22 or FIG. 23. However, a dry haemostatic agent H(e.g., a powder) may have improved deployment performance using theembodiment of FIG. 23. In so doing, the dry agent may be mixed with airand ‘blown’ into target site 182 by a mixture of powdered haemostaticagent H and air.

FIG. 24 shows a procedure 500 introducing an inking agent (representedby arrows I) to target site 182 through valve 43 and fluid conduit 42.An inking syringe 510 includes inking agent I, e.g. methylene blue, thatpervades tissue and marks it for later visualization. In the case ofmethylene blue, inked tissue is, for at least a predetermined timeperiod, semi-permanently marked by coloration. Thus, a surgeon mayeasily and directly identify the marked tissue when excised from targetsite 182. Stains other than methylene blue may be selected, including,for example, bismarck brown, carmine, coomassie blue, ethidium bromide,nile blue, or rhodamine. The selection of stain will primarily depend onthe type of tissue targeted for stain and the method of observation,e.g., direct visualization with natural light, indirect visualization,visualization with ultraviolet light, etc.

FIG. 25 shows an inked margin region 518 around the periphery of targetsite 182 with outer cannula 24 removed. A boundary 519 defines a depthof inked margin region 518, which is dependent upon the type of inkingsubstance used. For example, methylene blue may be used as an inkingsubstance and will penetrate the tissue surrounding target site 182 atleast a millimeter from the surface. The depth of penetration of theinking substance also may depend upon a number of factors including thetissue type, the dilution of the inking substance, the presence ofbleeding at target site 182, etc.

Referring to FIGS. 26-28 and 30, inking and resection of tissue isdiscussed. A pathologist uses the resected tissue to verify the marginis a clear margin or a clean margin, e.g., the margin tissue does notcontain cellular material that is considered pathologically diseasedand/or cancerous. An inked portion of tissue, and particularly,partially inked portion 541 (described below) is used wherein the inkedside indicates to the pathologist that the inking is on the side closestto the aggressively resected area. Thus, the pathologist knows that theinked portion is more likely to contain cancerous material, if any.

FIG. 26 shows further resection of target site 182, including inkedmargin region 518. A vacuum is drawn (see FIGS. 15-17) and tissue isresected from target region 182 as a prolapsed section 550 of tissueenters the cutting region. Thus, resection apparatus 50 is takingfurther tissue from target site 182 into inked margin region 518. Astissue is resected, it is subsequently collected in a collectioncanister such as, for example, a system as described in U.S. patentapplication Ser. No. 11/132,034, entitled “Selectively Openable TissueFilter,” filed May 18, 2005, to Joseph L. Mark et al., which is hereinincorporated by reference in its entirety. Thus, when inked marginregion 518 is resected, the tissue is held for inspection by the surgeonand pathologist.

FIG. 27A shows a fully inked portion 540 of resected tissue. As shown,the entire portion of tissue resected is inked with inking agent I.Thus, when viewed by the surgeon, it is known that the resected fullyinked portion 540 is taken from inked margin region 518.

FIG. 27B shows a partially inked portion 541 of resected tissue thatincludes an inked portion 542 and a non-inked portion 544. As shown,half of the resected tissue is inked while the other half is non-inked.When performing tissue resection, the surgeon may conclude from thisportion of tissue that inked margin region 518 is being resected throughthe thickness inking. Thus, resection of inked margin region 518 isbeing visually identified and verified through the collection ofresected tissue once a pathologist has confirmed that the sampledtissue, e.g. inked margin region 518, does not contain cancerous cells.

FIG. 27C shows a fully non-inked portion 546 of resected tissue.

FIG. 28 shows target site 182 after inking and resection to remove inkedmargin region 518 (see FIG. 26). After tissue has been resected to anextent such that no inked tissue remains within target site 182, themargin is achieved, and a margined cavity 560 remains.

FIG. 29 is a flow diagram of a resection process 1000, includingapplication of haemostatic agent H (see FIGS. 22-23) as is describedabove with respect to FIGS. 22 and 23. Resection process 1000 is usedwith inking methods described herein to confirm with pathology thatsignificant margins have been realized and that no cancerous cells aredetected within the margin region. Moreover, using the inking process, apathologist is able to determine which side of the resected tissue waspositioned inward toward target site 182. Resection process 1000 startsat step 1010 wherein the target site 182 is defined via the imagingmodality. The imaging modality chosen provides an image of generaltarget area 610 (such as in FIG. 33 wherein a lesion 620 is apparentwithin general target area 610). In this way, the surgeon has a visualimage of general target area 610 and can decide on a course of actionfor access and treatment. Control then proceeds to step 1020.

At step 1020, general target area 610 is localized using introducersystem outer cannula 24 (explained below in detail with respect to FIG.31 and steps 1910 through 1940). In general, the surgeon inserts andpositions outer cannula 24. Thereafter, the surgeon selectively insertsdistal end 46 of target confirmation device 26 to determine the positionof outer cannula 24 with respect to general target area 610. Using theimaging modality, the surgeon may be provided real-time guidance (in thecase of ultrasound imaging) or selective snapshots (in the case of MRI).In any case, the image provided by the imaging modality is used tolocalize outer cannula 24 such that treatment is appropriatelypositioned with respect to general target area 610. In a final step, thesurgeon confirms the position of outer cannula 24 with respect togeneral target area 610 (explained above in detail with respect to FIGS.12-14 and localization of target tissue 80). Control then proceeds tostep 1030.

At step 1030, tissue is aggressively resected at visible areas of thetumor at target site 182 using resection apparatus 50 (discussed indetail with respect to FIG. 16). Ideally, the resection operation willremove the entirety of any remaining lesion tissue. However, in manycircumstances, resection of a lesion carries the risk that not all ofthe lesion tissue will be resected. Control then proceeds to step 1040.

At step 1040, haemostatic agent H is applied to target site 182(discussed above in detail with respect to FIGS. 22 and 23). Haemostaticagent H prevents or otherwise reduces the amount of bleeding in targetsite 182 (see FIGS. 22-23). With haemostatic agent H applied, film 408reduces bleeding and prevents target site 182 from accumulating bodilyfluids, including blood. Such a reduction in fluid collection improvesthe efficiency of secondary treatments to target site 182. Control thenproceeds to step 1050.

At step 1050, resection apparatus 50 is removed from outer cannula 24(see FIG. 17). Note that step 1050 may also be performed before step1040. Control then proceeds to step 1060.

At step 1060, treatment tip 102 is inserted to the appropriate depth totarget site 182 through outer cannula 24 (see FIG. 18). It is importantto note that the therapy need not be provided by treatment device 100(See FIG. 7). For example, treatment may be provided by cryoprobe 102′(see FIGS. 7-9), light therapy 102″ (see FIG. 10), or electro 102′″ (seeFIG. 11). Further, as described below, treatment provided through outercannula 24 may include for example external beam HIFU therapy,interstitial HIFU therapy, electroporation therapy, ultrasonicporationtherapy, or interstitial microwave therapy. Control then proceeds tostep 1070.

At step 1070, a vacuum is applied to target site 182 via outer cannula24 (see particularly FIGS. 19A and 19B). This process is described indetail above with respect to FIGS. 18-21. In addition to the vacuumbeing applied to pull tissue close to treatment tip 102, wherehaemostatic agent H is applied to target site 182, greater collapse ofthe cavity in a uniform manner will be realized because target site 182is better sealed due to reduced bleeding. Control then proceeds to step1080.

At step 1080, treatment tip 102 is energized and ablation occurs withintarget site 182 (discussed above in detail with respect to FIGS. 20A and20B). Using haemostatic agent H, less blood will be present, and/orcoagulated, at target site 182. Thus, blood is not available as aninsulator around treatment tip 102. Therefore, more energy istransferred to the surrounding tissue and is more concentrated at marginregion 518. Control then proceeds to step 1090.

At step 1090, target site 182 is inked and tissue is resected using aquadrant approach. That is to say, when using an aperture-basedresection device, the aperture is rotated such that samples are taken inquadrants. In another example, the aperture may be rotated at twelve(10) o'clock, three (3) o'clock, six (6) o'clock, and nine (9) o'clock.In this way, multiple samples are taken from target site 182 at themargin. Control then proceeds to step 1092.

At step 1092, the resected tissue is then verified by pathology that theinked portions do not include cancerous tissue. If cancerous tissues arefound in the resected tissue, control then proceeds to step 1030 andaggressive resection may begin again with further treatment required. Ifcancerous tissue is not found in the resected tissue, e.g. the margin isclear, resection process 1000 then ends.

FIG. 30 shows a margin process 1100 for determining whether marginregion 518 has been resected (see FIGS. 24-28 for detailed descriptionsof margins resection). Margin process 1100 begins at step 1110 wheretarget site 182 is defined via the imaging modality. In this way, theimage guided therapy allows a surgeon to determine the success orthoroughness of the treatment at any stage, to determine that moretreatment is necessary, or that treatment is complete. Control thenproceeds to step 1120.

At step 1120, general target area 610 is localized using introducersystem outer cannula 24 (explained below in detail with respect to FIG.31 and steps 1910 through 1940). In general, the surgeon inserts andpositions outer cannula 24. Thereafter, the surgeon selectively insertsdistal end 46 of target confirmation device 26 to determine the positionof outer cannula 24 with respect to general target area 610. Using theimaging modality, the surgeon may be provided real-time guidance (in thecase of ultrasound imaging) or selective snapshots (in the case of MRI).In any case, the image provided by the imaging modality is used tolocalize outer cannula 24 such that treatment is appropriatelypositioned with respect to general target area 610. In a final step, thesurgeon confirms the position of outer cannula 24 with respect togeneral target area 610 (explained above in detail with respect to FIGS.12-14 and localization of target tissue 80). Control then proceeds tostep 1130.

At step 1130, tissue is aggressively resected at visible areas of thetumor at target site 182 using resection apparatus 50 (discussed indetail with respect to FIG. 16). Ideally, the resection operation willremove the entirety of any remaining lesion tissue. However, in manycircumstances, resection of a lesion carries the risk that not all ofthe lesion tissue will be resected. Control then proceeds to step 1140.

At step 1140, haemostatic agent H is applied to target site 182(discussed above in detail with respect to FIGS. 22 and 23). Haemostaticagent H prevents or otherwise reduces the amount of bleeding in targetsite 182 (see FIGS. 22-23). With haemostatic agent H applied, film 408reduces bleeding and prevents target site 182 from accumulating bodilyfluids, including blood. Such a reduction in fluid collection improvesthe efficiency of secondary treatments to target site 182. Control thenproceeds to step 1150.

At step 1150, the cavity at target site 182 is sampled. Using resectionapparatus 50, samples of tissue are resected from inked margin region518 and collected in a collection canister (or other suitable filter orcontainment apparatus). At this time, the surgeon checks the resectedtissue to determine what type of tissue is being resected, and candistinguish between the location of the resected tissue as it was takenfrom inked margin region 518. For example, a surgeon may see fully inkedportion 540, partially inked portion 541, fully non-inked portion 546,or a mixture thereof (see FIGS. 27A-27C) in the collection canister.When, for example, the resected tissue conforms substantially with fullyinked portion 540, the surgeon knows that inked margin region 518 is inthe process of being resected. When, for example, the resected tissueconforms substantially to partially inked portion 541, the surgeon knowsinked margin region 518 is close to being fully consumed in the areathat tissue-receiving opening 60 is exposed to at target site 182 (SeeFIG. 4). Additionally, for example, when the resected tissue appearslike fully non-inked portion 546, then the surgeon knows that inkedmargin region 518 is substantially removed at the location wheretissue-receiving opening 60 is exposed.

It is also important to note, that tissue-receiving opening 60 may berotated and translated about distal end 38 of outer cannula 24, suchthat the full extent of margin region 518 is resected (see FIGS. 15-17).Otherwise, for example, were a surgeon to leave resection apparatus 50in a fixed position (necessarily providing that tissue-receiving opening60 is in a fixed position), only prolapsed region 550 would be resectedand the remainder of inked margin region 518 would remain. Control thenproceeds to step 1160.

At step 1160, a check is performed to determine whether inked tissue isstill being resected. The surgeon observes the resected tissue fortissue marking resembling fully inked portion 540, partially inkedportion 541, and fully non-inked portion 546 (see FIGS. 27A-27C). If theresected tissue resembles fully inked portion 540 and/or partially inkedportion 541, then the surgeon can infer that inked margin region 518 isstill at least partially intact and that more resection is necessary. Onthe other hand, if the tissue resected fully or substantially resemblesfully non-inked portion 546, then the surgeon can infer that inkedmargin region 518 has been removed and that only margined cavity 560remains (see FIG. 28). However, it is important to note that thedetermination that only margined cavity 560 remains should be inferredwhere the surgeon has rotated tissue-receiving opening 60 and sampled atvarious areas of inked margin region 518 to ensure that not only aportion of inked margin region 518 has been sampled. If inked tissue isstill being resected, control proceeds to step 1150. Otherwise, controlthen proceeds to step 1170.

At step 1170, a favorable pathology has been achieved as indicated bythe lack of inked tissue being resected. At this point, inked marginregion 518 is removed and margined cavity 560 has been created. Thus,the margin has been achieved through a method of inking a cavity,resecting the cavity tissue, and determining whether the inked tissuehas been removed. Margin process 1100 then ends.

As an alternative to using inks, contrast agents may also be used intherapy delivery and treatment. In one example, nanoparticles may beused to highlight cancerous cells in large scale including tumors andmasses, using a selected imaging modality such that the therapy may beimage guided and/or image verified (explained in detail with respect toFIGS. 29-36). For example, magnetic resonance imaging can be used withcontrast agents including monocrystalline iron oxide nanoparticles(MIONs). The MIONs are in brief, iron oxide superparamagneticnanoparticles that are encased in dextran. In an enhanced mode,cross-linked iron oxide nanoparticles (CLIOs) may be used. In use,molecules such as transferin may be attached to MIONs and CLIOs suchthat the molecules “home-in” on cells (e.g., selectively target cells)having higher than normal metabolic activity. In this way, the MIONs andCLIOs accumulate in the cancerous cells. Then, under magnetic resonanceimaging, the cancerous cells and tumors may be identified by anincreased imaging response. In another example, ferumoxtran-10 may beused as a nanoparticle contrast agent for magnetic resonance imaging.

Additionally, smart contrast agents may be employed that have specialproperties in that they are not detectable using magnetic resonanceimaging until they have reached the target site. In one example, smartagents may encapsulate gadolinium within the delivery molecule andprotect the gadolinium from water protons rendering the gadoliniumeffectively inert to magnetic resonance imaging. When the intendedtarget (an enzyme or cellular ion) interacts with the delivery module,the interaction between water and gadolinium is allowed, resulting inchanges in T1 relaxation that can be detected by magnetic resonanceimaging. One example of a smart contrast agent is EgadMe (EgadMe being achelated gadolinium caged by a galactopyranose molecule). EgadMe allowsinteraction of water with the caged gadolinium when EgadMe comes incontact with a β-galactosidase enzyme.

Beyond gadolinium, which may only remain in tissue for approximatelythirty minutes, longer lasting contrast agents such as ferumoxtran-10may be preferred in that they may allow multiple imaging sequences andtreatment with a single dose. Gadolinium agents may require multipledoses during a procedure and may also give false readings due to newlesions created by the treatment due to traumatized tissue (e.g.,additional doses of gadolinium agents may seek out lesions created bytreatment rather than cancerous cells). On the other hand,ferumoxtran-10 allows an iron particle to enter a cell and the imagingis not degraded by additional doses or treatment related trauma.Depending upon the situations at hand, longer lasting contrast agents orgadolinium may be preferred depending upon the particular advantagesassociated with use.

Moving now to image directed therapy and image guided localization,FIGS. 31 and 32 show processes that include image directed therapy andimage guided localization. FIGS. 33-36 show certain steps of theseprocedures and should be reviewed in concert with FIGS. 31 and 32.

FIG. 31 shows a contrast agent localization process 1900 whereincontrast agents are used in conjunction with imaging modalities andtarget confirmation device 26 to verify therapy positioning. Using theimaging modality, e.g., MRI, PET, CT, ultrasound, terahertztechnologies, etc., the location of lesion 620 is more particularlydetermined with the use of a contrast agent. Moreover, combinations ofimaging modalities may be used together. In so doing, the location ofouter cannula 24 is precisely determined such that therapy may bedelivered accurately. Because contrast agents are not present wheretissue has already been resected, i.e. there is no agent in an emptyspace created by a cavity, target confirmation device 26 may be used tolocalize lesion 620. Moreover, even where a contrast agent was appliedto the margins of lesion 620, tissue resection may have removed thecontrasted portions of the cavity wall. Contrast agent localizationprocess 1900 begins at step 1905 where a contrast agent is introduced togeneral target area 610 and allowed to associate with lesion 620.Control then proceeds to step 1910.

At step 1910, outer cannula 24 is inserted within general target area610 in an attempt to locate target 48′ centrally within lesion 620.Generally, an introducer cannula, e.g. outer cannula 24, may be insertedto an approximate location and may then be further inserted, pulledback, or re-directed as required by contrast agent localization process1900. Control then proceeds to step 1920.

At step 1920, target confirmation device 26 is inserted through outercannula 24 to lesion 620 (see FIGS. 14, 33 and 34). Target confirmationdevice 26 (described in detail above with respect to FIGS. 3, 3A, 3B,and 14) is selected such that it is visible under the chosen imagingmodality. Control then proceeds to step 1930.

At step 1930, the selected imaging modality, in conjunction with anappropriate contrast agent, is used to determine whether targetconfirmation device 26 is in the correct position. In an embodiment, ananotechnology contrast agent is used to emphasize lesion 620 such thata lesion becomes apparent in the imaging modality chosen. Control thenproceeds to step 1940.

At step 1940, the position of target confirmation device 26, alsoviewable under the imaging modality, is then compared with lesion 620that is emphasized with the contrast agent. Using the contrast agent andtarget confirmation device 26, the position of lesion 620 as well as theposition of target confirmation device 26 is enhanced and may be moreeasily determined. If outer cannula 24 is correctly positioned, e.g.target confirmation device 26 is centrally located within lesion 620,then control proceeds to step 1950. Otherwise, control proceeds to step1910 where outer cannula 24 is repositioned.

At step 1950, target confirmation device 26 is removed from outercannula 24. Control then proceeds to step 1960.

At step 1960, a therapy instrument is inserted through outer cannula 24to lesion 620 and therapy is performed (see FIGS. 15-21). It isimportant to note that the therapy delivered may be the therapiesdescribed above including, but not limited to, resection, ablation(including electrode, photonic, and cryogenic ablation), delivery oftherapeutic agents, margin determinations, HIFU therapy, electroporationtherapy, ultrasonicporation therapy, interstitial microwave therapy, andany combination thereof. By particularly locating lesion 620 using acontrast agent, target confirmation device 26 may be preciselypositioned to lesion 620 or to the centralized mass of diseased tissuesuch that delivery of the therapy is more precise. Further, contrastagent localization process 1900 may be used multiple times in the sameclinical session if more than one target site has been identified orwhere more target sites are further identified during the sessionthrough the use of a contrast agent. In this way, the specific locationof lesion 620 is found and therapy is delivered precisely. Contrastagent localization process 1900 ends.

FIG. 32 shows a contrast agent therapy verification process 2000 whereinlesion 620 is identified, treatment is performed, and treatment isverified using a selected imaging modality. At least in the case of FIG.32, the therapy instrument is not limited to the specific embodiments oftreatment device 100 but may also include the resection of tissue.Contrast agent therapy verification process 2000 begins at step 2005where a contrast agent is introduced to general target area 610 andallowed to associate with lesion 620. Control then proceeds to step2010.

At step 2010, outer cannula 24 is inserted to lesion 620. Generally, anintroducer cannula, e.g. outer cannula 24, may be inserted to anapproximate location and may then be further inserted, pulled back, orre-directed as required by contrast agent therapy verification process2000. Control then proceeds to step 2020.

At step 2020, target confirmation device 26 is inserted through outercannula 24 to lesion 620. Target confirmation device 26 (described indetail above with respect to FIGS. 3, 3A, 3B, and 14) is selected suchthat it is visible under the chosen imaging modality. Control thenproceeds to step 2030.

At step 2030, the selected imaging modality, in conjunction with anappropriate contrast agent, is used to determine whether targetconfirmation device 26 is in the correct position. In an embodiment, ananotechnology contrast agent is used to emphasize lesion 620 such thata lesion becomes apparent in the imaging modality chosen. Control thenproceeds to step 2040.

At step 2040, the position of target confirmation device 26, alsoviewable under the imaging modality, is then compared with lesion 620that is emphasized with the contrast agent. Using the contrast agent andtarget confirmation device 26, the position of lesion 620 as well as theposition of target confirmation device 26, are enhanced and may be moreeasily determined. If a localizing obturator is correctly positioned,e.g. target confirmation device 26 is centrally located within lesion620, then control proceeds to step 2050. Otherwise, control proceeds tostep 2010 where outer cannula 24 is repositioned.

At step 2050, target confirmation device 26 is removed from outercannula 24. Control then proceeds to step 2060.

At step 2060, treatment device 100 is inserted through outer cannula 24to lesion 620 and therapy is performed. For more detail, see FIGS. 9,15-21, and 35. Control then proceeds to step 2070.

At step 2070, treatment device 100 may be removed; see also FIG. 35.Depending upon the type of therapy being performed and the imagingmodality selected, the removal of the therapy instrument may be requiredfor step 2080. However, some therapies, such as delivered therapeutics,may not require removal of the therapy instrument. Control then proceedsto step 2080.

At step 2080, the delivered therapy is verified using the imagingmodality selected; see also FIG. 35. In one example, cryoablation isverified where the ablated area, that originally had been highlightedwith the contrast agent, is now a signal void. In general, and whenusing a contrast agent to confirm therapy, an adjuvant therapy destroystissue at least one (1) millimeter beyond the resected cavity wall.Thus, image verified therapy can test to detect whether an adjuvanttreatment has destroyed tissue that contained marking agents or inkingagents. By directly observing the results of therapy, extent of theablation, the completeness of treatment may be determined. In anotherexample where the therapy includes resection, the extent of resectionmay be directly determined. After substantial resection has taken place,the extent of resection of the tissues highlighted by the contrast agentcan be visualized to directly determine whether all of the contrastagent has been removed. In this way, the surgeon determines whether moreresection is necessary (e.g., if contrast enhanced regions still existafter resection) or whether the resection was complete (e.g., where nohighlighted regions still exist at target site 182). Control thenproceeds to step 2090.

At step 2090, a determination is made as to whether continued therapy isrequired. If continued therapy is required, control proceeds to step2060. Otherwise contrast agent therapy verification process 2000 ends.

FIG. 33 shows a first attempt to position outer cannula 24 centrallywith respect to lesion 620. Using distal end 46 of a localizingobturator, the location of outer cannula 24 relative to lesion 620 isprecisely determined. Generally, the object of positioning outer cannula24 is to place distal end 38 centrally within lesion 620 such thatimproved tissue section and improved delivery of adjuvant therapy isaccomplished. However, a surgeon may desire distal end 38 in anylocation that treatment is desired. In this instance, distal end 38 isdesired to be placed centrally to lesion 620 such that lesion 620 may bedebulked or treated.

The placement of target 48′ to lesion 620 in FIG. 33 shows a missedplacement attempt. This is determined when lesion 620, outer cannula 24,and target 48′ are imaged. When lesion 620 is missed or the surgeondetermines a different position is necessary, outer cannula 24 isrepositioned. For example, such repositioning may occur as described indetail above with respect to FIG. 29, step 1020; FIG. 30, step 1120;FIG. 31, steps 1910-1940; and FIG. 32, steps 2010-2040.

Before target 48′ is correctly positioned, e.g., in the position thattreatment is desired, a number of image guidance verification steps andsubsequent repositioning of outer cannula 24 may be required. Wheremagnetic resonance is chosen as the imaging modality, the patient ismoved inside the bore to image and moved outside the bore forrepositioning of outer cannula 24 as well as treatment. The patient maybe subsequently placed back in the bore for further imaging to confirmlocation and treatment.

Alternatively, a real-time guidance approach may be taken when, forexample, ultrasound is chosen as the imaging modality. In this case, thesurgeon sees the placement target 48′ while locating outer cannula 24,for example, when distal end 46 includes features of a stylet such as atrocar tip.

FIG. 33A shows a portion of FIG. 33 in greater detail. Target 48′ iscross-shaped for easy identification (e.g., the cross-shape is quicklyrecognizable because it is not a natural anatomical shape). Further,target 48′ may be a material that is recognizable to the imagingmodality being used. Additionally, target 48′ may contain a contrastagent that provides greater response to the imaging modality than normaltissue. This allows the location of target 48′ to be quickly andaccurately determined.

Alternatively, target 48′ may provide a signal void when used withcertain imaging modalities (e.g., MRI). In this case, target 48′ willappear as a dark cross in the image. This is helpful for identificationpurposes when, for example, lesion 620 has been treated with a contrastagent. Thus, the identification of target 48′ is improved where lesion620 provides a high response and where target 48′ appears as a signalvoid.

Target confirmation device 26 is used in these cases as a localizingobturator for outer cannula 24. Thus, the primary use of targetconfirmation device 26 is to confirm initially where resection apparatus50 or an ablative device (e.g., electrode, photonic, and cryogenicablation) will be placed relative to lesion 620, when the device isinserted through outer cannula 24. In other words, the use of targetconfirmation device 26 with an imaging modality confirms that treatmentwill be placed where it is intended. Further, the confirmation isperformed using materials for outer cannula 24, target confirmationdevice 26, and target 48′ that are friendly and usable with a selectedimaging modality without distortion of artifact that would otherwisereduce the surgeon's ability to determine the location of target 48′relative to lesion 620.

FIG. 34 shows a center-of-mass placement of target 48′. In this case,placement of distal end 38 is confirmed by using an imaging modality tocompare the location of target 48 and lesion 620. Once confirmed, thesurgeon removes target confirmation device 26 from outer cannula 24 andinserts a therapy device, which may include a resection device. Theconfirmed position of outer cannula 24, and thus distal end 38, allowsfor precisely positioned therapy at lesion 620. Further, aggressivetherapies may be employed because the position is known and confirmed.Thus, because the position of outer cannula 24 is confirmed using animaging modality, it is known that the therapy will employed at lesion620.

FIG. 35 shows a partially treated region 630 within lesion 620. At thisstage, therapy has been applied near the center of lesion 620, resultingin partially treated region 630. As shown, the therapy device (used todelivery the therapy to lesion 620) has been removed for clarity. Thetherapies employed may include treatment by therapeutic agents,resection, or other therapies described herein. For detailed examples oftherapy employment at lesion 620, see above FIGS. 9, 15-21; FIG. 29,step 1060; FIG. 30, step 1030; FIG. 31, step 1960; and FIG. 32, 2060.

Turning now to additional types of therapies, the methods disclosedherein are applicable to more than just electrode, photonic, andcryogenic ablation. For example, the methods disclosed herein may alsobe used with external beam high intensity focused ultrasound (HIFU),electroporation therapy, ultrasonicporation therapy, and interstitialmicrowave therapy. These therapies include the use of radiofrequencyelectrodes, microwave antennas, laser fiberoptics, and ultrasoundtransducers. Each of these therapy modalities may be provided in aminimally invasive manner.

External beam HIFU therapy includes a specialized ultrasound probe thatis placed near lesion 620. The specialized ultrasound probe is deployeddown outer cannula 24 and placed near lesion 620. The surgeon then viewslesion 620 on an ultrasound monitor and maps the areas of concern basedon the ultrasound image and possibly through the use of a targetedcontrast agent. After the trouble regions are located and identified,the surgeon uses at high intensity ultrasound beam that is focusedthrough the specialized ultrasound probe to the precise areas, e.g.lesion 620, that require treatment. The high intensity ultrasound beamgenerates high heat a the focused area that destroys the tissue in anablative manner. Moreover, because the heat from external beam HIFUtherapy is transmitted directly to the tissue, it is possible also totreat the tissue directly adjacent to lesion 620, and in this way,create a margin using the therapy process itself.

In an alternative treatment, electroporation therapy is a highlytargeted method of delivering therapeutic drugs and/or compoundsdirectly to cells. A specialized probe, typically having electrodes, isdeployed along outer cannula 24 at lesion 620. By briefly applying anelectric field to the cell, a hole opens in the cell wall temporarily.This temporary opening allows therapeutics to enter the cell, andafterwards, the cell wall closes. The opening and closing of the cellwall occurs without permanently damaging the cell. However, aftertherapy, the therapeutics delivered are now trapped within the cell andmay kill the cell, if desired. This method is desirable for thetreatment of tumor cells, wherein the tumor cells are treated withchemotherapeutic drug molecules. The nature of electroporation allowsthese drugs to enter the tumor cell, resulting in enhanced cytotoxiceffects.

Alternatively, ultrasonicporation therapy is used which operates withsimilar principles to electroporation therapy, except that the probeuses ultrasonic energy to drive the therapeutic molecules. The drivingeffect increases absorption by the cells. The ultrasound energy alsoincreases the depth and dispersion to which the therapeutics aredelivered in lesion 620.

Moreover, interstitial microwave therapy may be deployed down outercannula 24 for treating lesion 620. The interstitial microwave therapydevice uses antennae to radiate microwave energy directly at a targetsite. Moreover, the interstitial microwave therapy may provide boththermal treatment (i.e., ablation through heating) as well as radiationtherapy, depending upon the configuration of the probe and thetransmitted frequencies.

FIG. 36 shows a completed region 640. At this phase, lesion 620 (fromFIGS. 33-35) is fully treated, leaving completed region 640. Animportant advantage of the therapy approach described herein is asignificant reduction in time to complete a therapy procedure. Lesion620 is debulked (e.g., resected) to reduce the volume of the tumor.Next, an adjuvant therapy, such as one of the therapies listed herein,is applied to the debulked region to improve the success of theresection procedure. Generally, these adjuvant therapies would have beenperformed in a stand-alone process that consumes substantially more timethan the procedures described herein. Further, these procedures areoften limited in effectiveness and are very painful. Thus, the methodsand apparatuses described herein reduce the time of the procedure,increase the effectiveness of adjuvant therapy delivered, and likelyreduce the pain associated with adjuvant therapy at least because theamount of time and number of visits is reduced.

In addition to the adjuvant treatments described above, it is alsopossible to resect tissue for modification and re-inject the modifiedtissue as a treatment. For example, resected tissue may be removed andconverted to denatured protein. FIG. 37 shows a re-injection process3000 that provides for removal of cancerous tissue, denaturing theprotein contained therein, and re-injecting the protein to stimulate thebody's natural immune response against the cancerous cells. Re-injectionprocess 3000 begins at step 3010 where tissue is resected and receivedby a collection canister (or other suitable filter or containmentapparatus). The process then continues at step 3020.

At step 3020 a specialist denatures the resected tissue. Denaturingtypically comprises altering a protein by a physical or chemical agentto reduce or deactivate its biological activity. The process thencontinues at step 3030.

At step 3030 the denatured protein is re-injected into the patient atthe target site. The denatured protein is no longer cancerous, but isforeign such that the body's immune system will respond. In this way,the denatured protein stimulates the body's immune system at the targetsite and provides that any cancerous cells that may be left over in themargin are targeted. In sum, the denatured protein is then re-injectedto the site of resection to trigger an immune response by the patients'body that would further attack cancerous cells. Thus, the cancerouslesion is removed, modified, and replaced as a type of protein thattriggers a natural immune response of the body that would then attackremaining cancerous cells, if any. This type of adjuvant treatment wouldfurther localize treatment to the location(s) that are most in need.Thus, whole-body treatments such as chemotherapy and radiation todestroy cancer cells would be reduced. Re-injection process 3000 thenends.

With respect to FIGS. 38-51, brachytherapy is introduced as an adjuvanttreatment to ensure a margin is created after tissue resection.Moreover, the brachytherapy discussed herein may also be used with otheradjuvant treatments (such as (resecting tissue, ablating tissue, heatingtissue, freezing tissue, applying chemicals to tissue, external beamHIFU therapy, interstitial HIFU therapy, electroporation therapy,ultrasonicporation therapy, and interstitial microwave therapy,described herein). Additionally, the method that brachytherapy isdelivered to a cavity may also be used in conjunction with a tissuemarker where the delivery vessel (e.g., a radioactive seed) may also beused as a tissue marker.

FIG. 38 shows placement of a localized treatment seed 702 (e.g.,brachytherapy) at target site 640. In general, treatment seed 702 isplaced at target site 640 after tissue is resected. Thus, using theapparatuses and processes described herein, a cavity is formed.Treatment seed 702 is placed in the cavity after tissue resection toprovide additional therapy directly at target site 640. In so doing,treatment seed 702 provides a high-dose of radiation, for example, tothe surrounding margin 704 at the inner periphery of target site 640.Because treatment seed 702 is placed directly at target site 640, themajority of radiation is directed to the margin 704 rather than broadlyexposing the surrounding healthy tissue.

Treatment seed 702 may be, for example, solid, sintered, or constructedas a binder material holding a radioactive agent. Alternatively, seed702 may be a plastic seed that has been coated with a radioactivesubstance. Seed 702 may also have a powder glued to the surface toprovide the treatment. Moreover, seed 702 may perform dual roles as asite marker that includes treatment material (e.g., radioactivematerial) to provide treatment at site 640.

FIG. 39 shows treatment from treatment seed 702 penetrating tissue 610to a treatment region 710. Treatment seed 702 is, for example, a pelletcontaining a predetermined amount of I-125. Those skilled in the artwill appreciate that the dose in time and the level of radioactivity ofseed 702 is adjustable depending upon the radioactive source materialand mass of said material included in seed 702. As FIG. 39 shows, seed702 provides radiation (not shown) through tissue 610 to a predetermineddepth 712. By providing the radiation directly to the tissue 610surrounding target site 640, a margin 704 of target site 640 is treated.There is a greater chance that if cancer cells were to remain aboutmargin 704, that the interstitial brachytherapy would apply treatmentdirectly to the remaining cancerous cells and destroy them. Treatmentregion 710 generally follows the inner surface of target site 640 topredetermined depth 712.

FIG. 40 shows placement of multiple treatment seeds 702 a, 702 b, 702 c,702 d at the inner periphery of target site 640. Multiple seeds 702a-702 d provide an option for interstitial brachytherapy to add seedshaving different properties, e.g. radioactivity, material, dose, etc. Inso doing, for example, seed 702 a may include a radioactive source thatprovides greater penetration into the tissue 610. Whereas, seed 702 bmay provide a longer-term dose, i.e. a longer time of release. Thus,each seed 702 a-702 d may be tailored to a specific goal of theinterstitial brachytherapy such that each seed 702 a-702 d may haveproperties allowing a plurality of predetermined treatment therapygoals. Seeds 702 a-702 d are generally placed around the insideperimeter of targets site 640.

FIG. 41 shows treatment penetrating tissue 610 including multiplelocalized treatment seeds 702 a-702 d. In contrast to the single-seedembodiment of FIG. 39, depth of penetration is somewhat uneven as thedepths of radiation penetration into tissue 610 are more pronounced neareach of seeds 702 a-702 d. Eventually the radioactive treatment ends dueto the dying-off of radioactivity from seeds 702 a-702 d. However, whereseeds 702 a-702 d are made from a lasting material, for examplepermanent site markers, seeds 702 a-702 d remain to be used foridentification of target site 640 in the future.

FIG. 42 shows an anchored localized treatment seed 720 within a patient.Rather than a free-floating treatment seed (shown in the precedingembodiments with respect to FIGS. 39-41), seed 720 is anchored to thepatient tissue 610 such that seed 720 can be placed in a specificlocation at target site 640 and may maintain that positioning to provideinterstitial brachytherapy. Anchored seed 720 includes a shaft 722projecting from the main body of seed 720 and includes barbs 724, 724′,724″ that are placed along a shaft. When shaft 722 is plunged withintissue 610, barbs 724, 724′, 724″ prevent, or at least substantiallyreduce the possibility of, seed 720 moving location at target site 640.In this way, seed 720 may be advantageously placed at target site 640 toprovide interstitial brachytherapy to a specific location at target site640.

Moreover, multiple anchored seeds 720 may be positively located at theperiphery of target site 640 to provide highly selective location of thetherapy. Anchored seed 720 may be end-deployed from a cannula using apushrod such as is described below in detail with respect to FIGS. 46and 47. However, anchored seed 720 may also be deployed in aside-deployment configuration wherein the pushrod holds seed 720 forapplying pressure against the interior wall of target site 640 forfixing attachment. In such a delivery embodiment, a pushrod may holdseed 720 with a predetermined mount of force and release seed 720 whenpulled away. In this way, seed 720 would be held while plunging barbs724 into tissue 640 and release once placed.

Referring now to FIGS. 43A-43B, cross-sections of a generallycylindrical seed 730 are shown. Seed 730 may be used for thebrachytherapy methods disclosed herein and comprises a generallycylindrical body having radioactive particles or granules 732 heldtogether in a binder 734. Granules 732 are typically chosen as rich inI-125 as a radioactive source in interstitial brachytherapy. However,other advantageous materials may be used for granules 732. Moreover, thesize and number of granules 732 may be adjusted accordingly to provide adesirable dose of radiation. Binder 734 may be a polymeric bindingsubstance or other substance that is generally impervious. In analternative embodiment, binder 734 may be biosorbable allowing forgranules 732 to be placed at target site 640 (described above) and thenessentially released from binder 734 when binder 734 is absorbed by thebody.

FIG. 43C shows a cross-section of a generally spherical seed 740 havinggranules 742. In contrast to the embodiment of FIGS. 43A-B, seed 740 isconfigured with granules 742 being generally evenly spaced apart withinbody 744. In so doing, the radiation pattern emanating from seed 740 isalso evenly distributed.

FIG. 44 shows a caged seed 750. In this embodiment, a radioactive seed88 is housed within a meshed body portion 752. Caged seed 750 may alsoused as a site marker for imaging under multiple modalities. Sitemarkers and deployment devices are described in detail in U.S. patentapplication Ser. No. 11/242,334, filed Oct. 3, 2005, to Michael E.Miller, et al., entitled “Site Marker Visible Under MultipleModalities,” the contents of which are incorporated by reference intheir entirety. Caged seed 80 may be constructed of a foam-likematerial. The foam-like material may be a carbon filled polymer or aglass filled polymer so as to be visible under multiple modalities. Inaddition, the foam-like material may contain therapeutic materials todeliver medication to the biopsy site. One exemplary material forconstruction of caged seed 750 is a thrombin filled polymer. Thefoam-like material acts as a matrix for tissue ingrowths.

FIG. 45 shows a caged seed 760 wherein a cage 752 includes barbs 768such that the cage and seed do not move once deployed. An outsidesurface 764 of a meshed body portion 762 is provided with one or morebarbs 768 disposed thereon. Barbs 768 assist in adhering therapeuticmarker 760 to internal walls of the biopsy cavity such as target site640 (described above). Barbs 768 are configured so as to extend at apredetermined angle relative to outside surface 764. In one specificembodiment, barbs 768 are configured to extend perpendicular to outsidesurface 764. In another embodiment, barbs 768 are positioned atdifferent angles relative to one another, including opposing oneanother.

FIG. 46 shows a compressed foam treatment 802 being delivered to targetsite 640. Foam treatment 802 is delivered through a cannula 806 using apush rod 804 to push foam treatment 802 through cannula 806 to targetsite 640. As discussed in detail below with respect to FIGS. 47-48, foamtreatment 802 is delivered in a compressed state and ultimately expandsto substantially fill target site 640. Foam treatment 802 is afoam-based medium that is treated with a therapeutic substance. Thetherapeutic substance may be a powdered radioactive material or acoating of radioactive material for providing interstitialbrachytherapy. However, the therapeutic material may also be a drug, ora combination of a drug and a radioactive material.

The foam-based medium is a biosorbable material, for example, collagenbased or a polyglycolic acid. Once delivered to target site 640, thebiosorbable material slowly dissolves and is absorbed by the body.Moreover, the material absorbs moisture from the body in order to expandto a larger volume (as shown in FIG. 48). In an alternative embodiment,the foam material may be a non-biosorbable material that is compatiblefor permanent placement in the body.

FIG. 47 shows foam treatment 802 at target site 640. Once pushrod 804 isextended beyond a distal end 805 of cannula 806, foam treatment 802 isdelivered to target site 640 which is typically a cavity created byresecting tissue. Foam treatment 802, and the therapeutic agent, may nowreact with the tissue surrounding target site 640.

FIG. 48 shows an expanded foam treatment 802 a in an expanded state andsubstantially filling target site 640. The nature of the foam-likematerial of foam treatment 802 a may expand naturally, may be triggeredfor expansion by body heat, may react with moisture at target site 640,or may absorb moisture at target site 640 to expand. Foam treatment 802a expands to fill a larger volume than when in the delivery state shownin FIGS. 46-47. As shown in FIG. 48, foam treatment 802 a substantiallyfills the volume of target site 640. In an alternative embodiment, foamtreatment 802 a may expand to fill target site 640 entirely such thatfoam treatment enlarges target site 640 (e.g., pushes against the wallsof target site 640) and is in pressing contact with the interior surfaceof target site 640 to provide treatment that requires contact withtissue. In the expanded state, foam treatment 802 a is also visibleunder multiple imaging modalities to ensure proper placement, expansion,and later location of target site 640. Although the foam-like materialmay be biosorbable, for at least a time the foam-like substance remainsand is identifiable using multiple imaging modalities.

FIG. 49 shows treatment penetrating the surrounding tissue of targetsite 640 where foam treatment 802 a is in an expanded configuration. Thetreatment penetrates to a depth 822 of the surrounding tissue in asubstantially uniform manner. In an embodiment, the treatmentpenetration is radiation from radioactive materials coated or infused tofoam treatment 802 a. In another embodiment, the treatment penetrationis due to a pharmaceutical or drug penetration delivered by foamtreatment 802 a. In yet another embodiment, the treatment penetration isboth a radiation and a pharmaceutical. Because foam treatment 802 asubstantially fills target site 640, the treatment is generally uniformin the tissue in contrast to the less uniform treatment distributionusing multiple seeds 702 a-702 d of FIG. 40.

FIG. 50 shows a deployment device 840 and placement of a treatment seedat the debulked target site 640. In contrast to the end-deployment ofFIGS. 46 and 47, deployment of seed 702 is performed in this embodimentthrough a side port 844. A pushrod (not shown) may deploy 842 down thecannula of deployment device 840 and out port 844. Deployment methods,apparatuses, and others, are described in detail in U.S. patentapplication Ser. No. 11/305,141, filed Dec. 16, 2005, to Terry D.Hardin, et al., entitled “Biopsy Site Marker Deployment Device,” thecontents of which are incorporated by reference in their entirety.

Side port 844 may be selectively rotated 850 to provide an orientationrelative to the inner periphery of target site 640 for targeteddeployment. That is, as shown in FIG. 50, seed 720 is deployed generallyto the top portion of target site 640. However, a user may rotate 850deployment device 840 such that side port 844 would deploy seed 702 tothe bottom portion of target site 640. In this way, the user mayselectively position side port 844 for the deployment of seeds 702 intarget site 640.

FIG. 51 shows a flow diagram of deployment and placement method 4000 ofone or multiple treatment seeds 702, and other treatment mechanismsdescribed herein, at the debulked target site 640. Deployment andplacement method 4000 in general provides that a cavity is created andbrachytherapy implants (e.g., seeds 702, and foam 802) are placed withintarget site 640 at a desired location. Deployment and placement method4000 begins at step 4010 where tissue is resected from target site 640.In this step, tissue is debulked in gross to remove, for example,suspected cancerous tissue. Other adjuvant therapies, such as thosedescribed herein, may be used once resection is complete. Moreover,methods of testing for removal of a margin may also be used, such as theinking method described herein. Once debulking and adjuvant therapy arecomplete, control proceeds to step 4020.

At step 4020, a brachytherapy deployment tool is inserted to target site640. In some instances, such as where end-deployment is preferred, theouter cannula of the resection device may be used as a deployment tool.(See FIGS. 46 and 47). Alternatively, the introducer cannula used forthe resection device may be used for end-deployment. Otherwise, aside-deployment tool (see FIG. 50) may be inserted in preparation ofdeployment of a brachytherapy seed or foam. Once the deployment tool isinserted, control proceeds to step 4030.

At step 4030, rotation of the deployment tool is performed such that thedeployment opening (see side port 844 of FIG. 50) is positioned in alocation for deployment. The positioning of the deployment opening willdetermine where the brachytherapy seed (e.g., seed 702) will bepositioned once deployed. Thus, the side opening is rotated to alignwith the intended location of delivery. Rotation of the deployment toolis not required or preferred when end-deployment is used.

Where multiple brachytherapy seeds are deployed (see step 4050 below),rotation is preferred at least such that brachytherapy seeds aredeployed at different positions within target site 640. For example,where four seeds are to be deployed (see FIG. 41 above), then thedeployment tool should be rotated ninety degrees (90°) with thedeployment of each seed to position the seeds spacedly within targetsite 640. Additionally, when a barbed device for maintaining positionwithin cavity 640 is used (see caged seed 760 FIG. 45 above) thedeployment opening (see side port 844 of FIG. 50) is of importancebecause the orientation of the opening will control where the seed isdeposited and will substantially remain in that position. Control thenproceeds to step 4040.

At step 4040, the brachytherapy implant is deployed. For example, apushrod is moved distally through the deployment device to push thebrachytherapy implant distally for end or side deployment. Controlproceeds to step 4050.

At step 4050, the user determines whether or not to deploy more (ormultiple) implants. For example, a single seed 702 is deployed in FIG.38. Alternatively, multiple seeds 702 a-702 d are shown deployed in FIG.40. Moreover, where a foam-type brachytherapy delivery is used, only asingle foam treatment 802 is deployed (see FIGS. 46 and 47). However,where treatment site 640 is a large cavity (e.g., having a largevolume), multiple foam treatments 802 may be deployed to fill the cavityif a single foam treatment 802 would not sufficiently fill the volumewhen expanded. If the user decides more implants should be deployed,control proceeds to step 4030. If no more implants are desired to bedeployed, control proceeds to step 4060.

At step 4060, the deployment procedure is finalized by removing thedeployment device from the patient. Deployment and placement method 4000then ends.

The present invention has been particularly shown and described withreference to the foregoing embodiments, which are merely illustrative ofthe best modes for carrying out the invention. It should be understoodby those skilled in the art that various alternatives to the embodimentsof the invention described herein may be employed in practicing theinvention without departing from the spirit and scope of the inventionas defined in the following claims. It is intended that the followingclaims define the scope of the invention and that the method andapparatus within the scope of these claims and their equivalents becovered thereby. This description of the invention should be understoodto include all novel and non-obvious combinations of elements describedherein, and claims may be presented in this or a later application toany novel and non-obvious combination of these elements. Moreover, theforegoing embodiments are illustrative, and no single feature or elementis essential to all possible combinations that may be claimed in this ora later application.

1. A method of establishing a margin region comprising: forming a cavityby resecting tissue, said cavity having an inner wall of tissue at adesired biopsy location; applying ink to at least a portion of saidinner wall of said cavity subsequent to forming said cavity, said inkpenetrating said tissue to form an inked tissue region at leastpartially defined by said inner wall and an inked tissue boundarylocated a distance from said inner wall, said inked tissue boundaryseparating said inked tissue from non-inked tissue; removing a tissuesample comprising at least a portion of said inked tissue boundary, andat least a portion of said inked and non-inked tissue; and determining apathology of said inked portion of said tissue sample.
 2. The method ofclaim 1, wherein said determining a pathology comprises testing saidinked tissue for cancerous material.
 3. The method of claim 1, furthercomprising: repeating applying ink to at least a portion of said innerwall of said cavity to form an inked tissue region having an inkedtissue boundary, removing a tissue sample comprising at least a portionof said inked tissue boundary, and determining a pathology of an inkedportion of said tissue sample, when the pathology of a previous tissuesample indicates diseased tissue is present within said inked portion ofsaid previous tissue sample.
 4. The method of claim 1, wherein saiddetermining a pathology comprises determining whether said inked portionof said tissue sample is clear of diseased material.
 5. The method ofclaim 1, further comprising: administering an adjuvant treatment.
 6. Themethod of claim 5, wherein said adjuvant treatment is selected from oneof: resecting tissue, ablating tissue, heating tissue, freezing tissue,applying chemicals to tissue, external beam HIFU therapy, interstitialHIFU therapy, electroporation therapy, ultrasonicporation therapy,interstitial microwave therapy, and brachytherapy.
 7. The method ofclaim 5, further comprising: inserting an adjuvant therapy device intosaid cavity; and applying a vacuum within said cavity whileadministering said adjuvant treatment, said vacuum causing said cavityto collapse around said adjuvant treatment device.
 8. The method ofclaim 5, further comprising administering a haemostatic agent to saidinner wall prior to administering said adjuvant treatment.
 9. The methodof claim 5, further comprising administering said adjuvant treatmentbefore applying said ink to said inner wall.
 10. The method of claim 5,further comprising administering said adjuvant treatment to said innerwall of said cavity before applying said ink to said inner wall.
 11. Themethod of claim 1, further comprising: administering a haemostatic agentto said cavity before applying said ink to said inner wall.
 12. Themethod of claim 11, further comprising administering an adjuvanttreatment to said inner wall of said cavity after administering saidhaemostatic agent to said cavity and before applying said ink to saidinner wall.
 13. The method of claim 1, further comprising locating aninked portion of said tissue sample determined to have been locatednearest to said cavity for testing.
 14. The method of claim 13, whereindetermining a pathology comprises testing said portion of said inkedtissue sample determined to have been located nearest to said cavity.15. The method of claim 1, further comprising removing a second tissuesample and determining the presence of inked tissue in said secondtissue sample, and repeating said step of removing said tissue samplewhen the second tissue sample is determined to have inked tissue.
 16. Atreatment method for improving an adjuvant therapy comprising: resectingtissue to form a cavity having surrounding tissue and an inner wall;applying a haemostatic agent to said surrounding tissue; applying anadjuvant therapy by an adjuvant therapy device to said surroundingtissue following application of said haemostatic agent; applying ink toat least a portion of said inner wall of said cavity followingapplication of said adjuvant therapy, said ink penetrating said tissueto create an inked tissue region at least partially defined by saidinner wall and an inked tissue boundary located a distance from saidinner wall, said inked tissue boundary separating said inked tissue fromnon-inked tissue; resecting a tissue sample from said surrounding tissueafter said applying said adjuvant therapy, said tissue sample includingat least a portion of said inked tissue boundary, and at least a portionof said inked and non-inked tissue; and determining whether said inkedportion of said tissue sample is clear of diseased material.
 17. Themethod of claim 16, further comprising: continuing to resect tissue toform a larger cavity if said inked tissue is determined as not clear ofdiseased material.
 18. The method of claim 17, further comprisingrepeating applying said haemostatic agent, applying said adjuvanttherapy, applying said ink to said inner wall, and resecting a tissuesample, when said determining a pathology indicates cancerous materialis present within said inked portion of said tissue sample.
 19. Themethod of claim 16, wherein the adjuvant therapy is selected from oneof: resecting tissue, ablating tissue, heating tissue, freezing tissue,applying chemicals to tissue, external beam HIFU therapy, interstitialHIFU therapy, electroporation therapy, ultrasonicporation therapy,interstitial microwave therapy, and brachytherapy.